1. Field of the Invention
This invention relates to an antithrombic vascular prosthesis composed of polytetrafluoroethylene and quaternized polyethyleneimine having heparin bound thereto.
2. Description of the Prior Art
Fabric prostheses composed of a knitted or woven fabric of Dacron or polytetrafluorethylene in the form of a tube having inner diameters that are relatively large are now being utilized with relatively good results. In particular, good results are generally obtained with vascular prostheses for arteries which have an inner diameter of at least about 7 mm. Despite this, few small inner-diameter arteries are clinically acceptable. In venous applications, small inner-diameter prostheses exhibit a lower patency rate than in arterial applications. The rate of blood flow in veins is smaller than in arteries, and to prevent thrombosis, it is important to inhibit platelet adhesion to the inner surface of the artificial veins. This requirement is not fully met by presently available artificial veins.
Some tubings made of stretched or expanded polytetrafluoroethylene have been demonstrated to be clinically useful as vascular prostheses for arteries and veins. This is described, for example, in Soyer et al., "A New Venous Prosthesis", Surgery, Vol. 72, page 864 (1972), Volder et al., "A-V Shunts Created in New Ways", Trans. Amer. Soc. Artif. Int. Organs, Vol. 19, p. 38 (1973), Matsumoto et al., "A New Vascular Prosthesis for a Small Caliber Artery", Surgery, Vol. 74, p. 519 (1973), "Application of Expanded Polytetrafluoroethylene to Artificial Vessels", Artificial Organs, Vol. 1, p. 44 (1972), ibid., Vol. 2, p. 262 (1973), and ibid., Vol. 3, p. 337 (1974), Fujiwara et al., "Use of Goretex Grafts for Replacement of the Superior and Inferior Venae Cavae", The Journal of Thoracic and Cardiovascular Surgery, Vol. 67, p. 774 (1974), and Belgian Pat. No. 517,415.
The results of these clinical experiments are summarized below.
When a suitable porous prosthesis is implanted as a conduit within the arterial system, the fine pores are clogged by clotted blood, and the inside of the prosthesis is covered with a clotted blood layer. The clotted blood layer is made up of fibrin, and the thickness of the fibrin varies, for example, according to the material of and the surface structure of the prosthesis. Since the thickness of the fibrin approaches 0.5 to 1 mm when a knitted or woven fabric of Dacron or polytetrafluoroethylene is used as the prosthesis, success is achieved only with those blood vessels which are not occluded due to this increase in wall thickness by the fibrin layer (that is, arteries having an inside diameter of 5 to 6 mm or more). Generally, knitted or woven prostheses having smaller inner diameters have not been successful.
A polytetrafluoroethylene tubing which has been stretched has a microstructure composed of very fine fibers and nodes connected together by the fibers. The diameters of the fibers vary depending on various stretching conditions, and can be made much smaller than fibers of the knitted and woven fabrics mentioned above.
It has been confirmed clinically that when a structure composed of fibers and nodes is expressed in terms of pore sizes and porosities, or fiber lengths and nodular sizes, a polytetrafluoroethylene tubing having a pore size of from about 2.mu. to about 30.mu. (pore sizes below about 2.mu. are undesirable), a porosity of about 78% to about 92%, a fiber length of not more than about 34.mu. (fiber lengths of about 40.mu. to about 110.mu. are undesirable), a nodular size of not more than about 20.mu., and a wall thickness of about 0.3 mm to about 1 mm exhibits a high patency rate without substantial occlusion by fibrin deposition.
It has been reported, however, that venous prostheses exhibit a much lower patency rate than arterial prostheses, and do not prove to be entirely satisfactory for prosthetic purposes. It has also been reported that when a vascular prosthesis has too high a porosity, a tearing of the prosthesis by the suture used in joining the prosthesis with the vessel of the patient tends to occur.
In the healing process after implantation, connective tissue first develops on the outer periphery of the polytetrafluoroethylene tubing and the tissue organizes, and afterwards the fibrin layer on the inner surface of the tubing organizes. At this time, a continuity of the intimas of the host's vessels with the neointima of the inner surface of the vascular prosthesis is established, and simultaneously, the fibrin layer is replaced by the fibrous tissue which has entered the prosthesis through the fine pores from the periphery of the prosthesis. Furthermore, after a certain period of time, the neointimas at the inner surface are connected firmly to the connective tissue lining the outer wall of the prosthesis, thereby completing the formation of an artery. It is known that this artery formation requires a period of usually about 4 to 6 months. It is known on the other hand that with vascular prostheses implanted in veins, the rate of entry of the connective tissue from the periphery thereof is slower than for arterial implantation.
However, despite these reported clinical results, reproducible, good results have not been obtained. A porous tubing of polytetrafluorethylene permits the adsorption of plasma protein. Platelets adhere to the adsorbed plasma protein to form fibrin fibers which capture blood corpuscles and become a fibrin deposited layer. This deposited layer is expected to subsequently form a pseudointima of the prosthesis. However, the fibrin deposited layer is frequently too thick, and insufficient nutrition of the pseudointima or neointima occurs. This will result in disconnection by necrosis or in thrombic occlusion of the inner surface of the prosthesis.